P1685: CHEMOTHERAPY-INDUCED ENDOTHELIAL DAMAGE AS UNDERLYING CAUSE FOR PERIPHERAL NEUROPATHY AND REDUCED METABOLISM IN STATIC PRESSURE-ADJUSTED COMPRESSION FOR CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHIES
Authors: A. Haspel, R. Rheimann, J. Mohammad, B. Lischke, H. Habazettl, J. A. Schmidt-Lucke, S. Ochsenreither, U. Keller, C. Schmidt-Lucke
Journal: HemaSphere (2022)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) as common side effect is caused by impaired microvascular neuronal perfusion as shown in animal models. In contrast, several authors unsubstantiate postulate reduced perfusion induced by compression therapy responsible for neuroprotection. We, thus, tested the hypothesis of chemotherapy-induced endothelial damage (CIED), increased microvascular perfusion and reduced metabolism in response to pressure-adjusted static compression (PSC) in patients undergoing chemotherapy (CTX) with and without CIPN. Aims: Aim of the study is to test the hypothesis of chemotherapy-induced endothelial damage (CIED), increased microvascular perfusion and reduced metabolism in response to pressure-adjusted static compression (PSC) in patients undergoing chemotherapy (CTX) with and without CIPN. Methods: Metabolic oxygen demand (dh), tissue oxygenation (StO2), oxygen supply (O2h) and microvascular perfusion (th) were measured with quantitative time-resolved near infra-red spectroscopy (NIRS) and temperature with thermography following standard procedures in CTX (n=22) with and without clinical CIPN (n=11 each, 46% male; age 64 ± 11 years) and compared to healthy controls (n= 20, 50% male; age 24.5 ± 4.3 years) and patients with peripheral arterial disease (PAD, 75% male, age 68 ± 9 years, 42%, positive controls) on upper extremities. Endothelial microvascular function was quantified during post-ischaemic reactive hyperaemia (PIRH). PSC was applied with commercially available compression products and patented palmar pads for up to 90 minutes under standardised and controlled conditions. Results: Patients with CTX with CIPN showed significant endothelial dysfunction compared to controls (StO2 downslope -7 ± 2%, T95(s) 13 ± 5, PIRH-AUC 9 ± 6, p<0.05 each) and CTX without CIPN (p<0.05 each), much like PAD. Significant reduction of skin temperature in healthy controls as well as CTX patients of 2°C to 6°C were achieved with PSC (p<0.05 each) and cryoapplication (up to -15°C, p<0.001). In controls, PSC instantly reduced metabolic oxygen demand of the intervened hand (dh: -4.6 ± 2.4%, p<0.05) that remained on a low level only influenced by opening of the capillary bed after 5 to 30 minutes (th: +5.6 ± 7.5%, p<0.01). Likewise, cryoapplication significantly decreased metabolic oxygen demand (p<0.05). In contrast to controls with constant increase of local tissue oxygenation (StO2: +11.2 ± 7.0%, p<0.001) for the entire 90 minutes driven by increased oxygen supply (O2h: +11.7 ± 7.3 µM/s, p<0.001) and microvascular perfusion (th: 7.6 ± 8.7%, p<0.005), patients with CTX showed significant reduced th and dh (p<0.05 each) only, but no increase of StO2 with PSC. Summary/Conclusion: Reduced local temperature and metabolic oxygen demand indicate metabolic reduction as an underlying mechanism of action of PSC. CIPN is associated with marked endothelial dysfunction comparable to PAD, hampering increase of O2-supply and microvascular tissue oxygenation in result to PSC. This indicates that optimisation of microvascular perfusion maybe a further player of the therapeutic effect of PSC. These finding open the field for well-designed RCT to develop novel treatment options for CIPN targeting CIED.